There is a huge disparity between the number of patients who need a transplant and the available organ donors. Pigs could readily resolve the unmet need. The physiology of many tissues is close to that of humans. They can be raised in clean controlled conditions. One potential drawback, however, is a virus defined in the porcine genome, PERV. In tissue co-culture with human cell lines, PERV may be transmitted to the human cells. There has not yet been demonstrated any infectious or pathogenic state in humans or animal models. PERV consists of three viruses: PERV A, PERV B and PERV C. PERV A and PERV C are the primary culprits for transmission to human cell lines. Our program has maintained a herd of very clean pigs for potential clinical xenotransplantation. Co-culture tests with liver cells from our pigs failed to pass the virus to human cells. Screening the pigs, they are PERV C negative. The majority are PERV A negative. One pig is negative for all three viruses as well as the generic gag/pol gene for PERV. This application will generate a herd of PERV free pigs. These pigs will be thoroughly evaluated for PERV by virologic methods. As a stringent test for possible infectivity, human cells will be cultured in utero in PERV free pigs. PUBLIC HEALTH RELEVANCE Organ transplants from pigs could be valuable in resolving the severe shortage of human organ donors. Some organs, such as hearts and pancreatic islets, are physiologically very similar to humans. Furthermore, pigs can be raised under very clean controlled conditions. However, concern has been raised about a virus present in pigs, porcine endogenous retrovirus (PERV). PERV is part of the DNA of the pig, so it cannot be eradicated by conventional means. A herd that has been maintained by us for clinical xenotransplantation has been found to have very little PERV. One pig appears to be PERV free. This application would produce a PERV free swine herd for clinical xenotransplantation.